1. Field of the Invention
The invention pertains to the field of miniaturized chemical and biochemical fluid management systems using microfluidic technology. In particular, the invention relates to the design and fabrication of reconfigurable microfluidic systems using discrete devices and other building blocks on a “breadboard” base.
2. Description of Related Art
The concept of the breadboard is well known to those familiar with electronics and electronic circuits. The term “breadboard” derives from the earliest days of electrical experimentation, when circuits were literally built on a base made from a wooden breadboard.
In the electronics lab, the breadboard system allows an investigator to quickly build a test version of a potentially useful circuit from discrete electronic components. The breadboard framework allows the experimenter to construct a circuit with minimum effort, subsequently enabling the testing of certain values at important locations in the circuit.
For an electronic circuit, voltage, current and resistance are important factors to be tested. The components are standardized—IC chips, resistors, capacitors, etc., often with a standardized spacing of connections. Once the circuit has been sufficiently tested, a copy can be made in a printed circuit board, or as a mass produced integrated circuit. The breadboard enables one to design and test novel circuits, and sub-circuits, while mitigating the prohibitively expensive process of producing multiple revisions in a mass production environment.
The breadboard concept is useful in developing integrated microfluidic systems as well. Instead of voltage, current and resistance, the variables governing microfluidic experiments are typically flow rate, pressure, and concentration, but the utility of easily reconfigured systems by the user is the same.
One of the most attractive features for developing microfluidic systems for life science research is the potential integration of a series of sequential operations on a single device. However, there are inherent difficulties for developing high efficiency, fully integrated microfluidic applications. First, to establish some baseline parameters for the design of an optimized device, sequential operations are preferably developed and characterized in a discrete manner before system integration. This discretization allows the developer to reduce a complex, multi-variable challenge into many smaller, manageable problems and tackle them individually. On the other hand, it is often impossible to test each section of a system in isolation before attempting integration; many components do not provide meaningful information until they are assimilated into the system as a whole. The demand to isolate the specific impact of an individual module in a sequential operation in addition to the ability to investigate the overall performance for the integrated device present an unmet challenge for microfluidic developers.
A framework for the compilation of modular microfluidic chips, i.e. a “microfluidic breadboard”, would allow the developers to test, alter and retest components in a synchronous fluid management environment which mimics the integrated device without the cost and delay of multiple complete system revisions. However, unlike electronics, there is no standardization of discrete microfluidic components which lend themselves to easy breadboarding, as do the standardized components and packaging of electronic components. Also, the routing of fluids encounters difficulties that are not presented when conducting electrons through wires in electronic circuits.
In an electronic breadboard, each of the components is supplied with leads that allow it to be wired into the system as a whole. In a fluid management system, tubes or channels must be provided to route the fluid through the system. Fluid leakage, chemical stability of the sealing materials, contamination and cross talk, capillary forces, and void volume must all be considered when designing microfluidic systems. This requires seals made from a material that is chemically compatible with the fluid retained by the system to provide adequate sealing at the required pressure. The seal and design of fluid passage between adjoining devices must prevent the fluid from escaping the intended route; it must do so with a minimum of swept volume in order to maximize the performance of the overall system.
Currently, the limited options to join discrete microfluidic components to form fluidic network are almost exclusively based on using epoxy with standard capillaries or “Nanoport” fittings made by Upchurch Scientific, a division of Scivex, Oak Harbor, Wash. While the former method is straightforward and widely utilized by many researchers, its cumbersome nature during the capillary and system assembly makes the process very tedious and time consuming. The length of capillary required to make connections increases the overall system length, resulting in higher flow resistances and difficulty when balancing the flow in parallel branches of a system. The complexity of such a capillary network scales up rapidly such that even in the integration of a modest number of microfluidic components, the “plumbing” would become excessively complex. Additionally, the components used in an assembled system are not readily reusable. NanoPort fittings do not suffer from all of the drawbacks of epoxy, but they require precision alignment to the fluid communication port of the microfluidic chip; aligning two 100 μm scale holes via a compressible ferrule is not at all trivial.
It is also important that optical access into the components of a system be maintained—that is, the individual devices or “chips” must not be obscured from view by the breadboard base or other fittings. Although the fittings that Upchurch Scientific provides are relatively small, in comparison to the chip scale devices to which they attach, they require a bonding area that can exceed the active device area of the fluidic chip. For this reason, there can be difficulties with obscuring the optical access to the active area of the chip. A method is required that allows devices to be easily placed and repositioned while minimizing interval volume as well as assuring optical and fluidic access.
Purcell's U.S. Pat. No. 3,548,849, “Fluidic Circuit Package”, discloses means of stacking fluidic components that provides for the synthesis of a microfluidic circuit. However, the stacking of chips, while making the sealing of the components simpler, eliminates the investigator's ability to monitor the system optically. The stacked scheme also restricts fluid delivery by limiting the available locations for ingress or egress. The purpose of Purcell's work was to provide a means for producing fluidic circuits in order to replace electronic circuits, not to allow for chemical and biochemical reaction and analysis.
Bard's U.S. Pat. No. 5,580,523, “Integrated Chemical Synthesizers” and Hahn's Published Application No. 2003/0012697 “Assembly Microchip Using Microfluidic Breadboard” disclose means for producing detachable microfluidic systems. In both of these cases, a “motherboard” structure is required to complete the transport of the fluid through the system. This “motherboard” comprises a series of channels in a substrate to which the chips are subsequently connected at predetermined locations. This scheme necessitates adherence to a set base pattern; the flexibility of the system is restricted by the “motherboard” design. The base pattern is predefined and limits the overall microfluidic network configurability.
Kennedy's U.S. Pat. No. 6,086,740, “Multiplexed microfluidic devices and systems” and O'Connor's published application No. 2002/0124896, “Modular microfluidic systems” outline two systems which are created for specific experiments. As in Bard, fluids in these systems are routed from devices through channels in the motherboards.